Ultrasound-mediated destruction of paclitaxel and oxygen loaded lipid microbubbles for combination therapy in ovarian cancer xenografts

Li Liu; Shufang Chang; Jiangchuan Sun; Shenyin Zhu; Minyue Yin; Yi Zhu; Zhigang Wang; Ronald X Xu

doi:10.1016/j.canlet.2015.02.052

Ultrasound-mediated destruction of paclitaxel and oxygen loaded lipid microbubbles for combination therapy in ovarian cancer xenografts

Cancer Lett. 2015 May 28;361(1):147-54. doi: 10.1016/j.canlet.2015.02.052. Epub 2015 Mar 6.

Authors

Li Liu¹, Shufang Chang², Jiangchuan Sun³, Shenyin Zhu⁴, Minyue Yin³, Yi Zhu³, Zhigang Wang⁵, Ronald X Xu⁶

Affiliations

¹ Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology, Chongqing 400016, China.
² Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address: shfch2005@163.com.
³ Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
⁴ Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
⁵ Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
⁶ Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA.

PMID: 25754815
DOI: 10.1016/j.canlet.2015.02.052

Abstract

We have synthesized multifunctional oxygen and paclitaxel loaded microbubbles (OPLMBs) for ultrasound mediated delivery of combination therapy in an ovarian cancer xenograft model. In comparison with other therapeutic options, intravenous injection of OPLMBs followed by ultrasound mediation yielded a superior therapeutic outcome. Immunohistochemical analyses of the dissected tumor tissue confirmed the increased tumor apoptosis and the reduced VEGF expression after treatment. Western Blot tests further confirmed the decreased expressions of HIF-1α and P-gp. Our experiment suggests that ultrasound mediation of OPLMBs may provide a promising drug delivery strategy for the combination treatment of ovarian cancer.

Keywords: Drug delivery; Microbubbles; Ovarian cancer; Oxygen; Ultrasound.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1
Animals
Antineoplastic Agents, Phytogenic / pharmacology
Apoptosis / drug effects
Apoptosis / radiation effects
Blotting, Western
Cell Proliferation / drug effects
Cell Proliferation / radiation effects
Combined Modality Therapy
Drug Delivery Systems*
Female
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Lipids / chemistry*
Mice
Mice, Inbred BALB C
Mice, Nude
Microbubbles
Ovarian Neoplasms / metabolism
Ovarian Neoplasms / pathology*
Ovarian Neoplasms / therapy*
Oxygen / metabolism*
Paclitaxel / pharmacology*
Tumor Cells, Cultured
Ultrasonics*
Vascular Endothelial Growth Factor A / metabolism
Xenograft Model Antitumor Assays

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Antineoplastic Agents, Phytogenic
Hif1a protein, mouse
Hypoxia-Inducible Factor 1, alpha Subunit
Lipids
Vascular Endothelial Growth Factor A
vascular endothelial growth factor A, mouse
Paclitaxel
Oxygen

Grants and funding

R21CA15977/CA/NCI NIH HHS/United States